Brain Cells Made From Skin of 80-Year-Olds With Lou Gehrig's

By Rob Waters

July 31 (Bloomberg) -- Researchers at Harvard University have made motor neurons, the brain cells that degenerate in patients with Lou Gehrig's disease, from skin cells taken from two elderly sisters with the condition.

The advance, published today in the journal Science, used a technique developed during the last two years that gives adult cells the same power as those from embryos to turn into any cell type in the body. The disease, also known as amyotrophic lateral sclerosis, or ALS, robs patients of muscular control and may eventually lead to paralysis.

The Harvard team took the first step toward fulfilling one of the promises of the new technology by creating lines of human stem cells from the tissue of patients with a genetic disease. The neurons created may, over time, show early signs of ALS, a disease that normally strikes people in their 50s and 60s, allowing researchers to study its workings and hunt for cures.

``We now have in the culture dish cells which have the same genetic make-up as do the patients,'' said Christopher Henderson, a researcher at Columbia University in New York and co-author of the study, on a call with reporters yesterday. ``They are the very cells that are affected in the disease. This provides us the opportunity to study these motor neurons and see whether they behave in a manner that mimics the disease.''

Yamanaka Method

The neural cells were derived by the team using a method first developed by Shinya Yamanaka, a researcher at Kyoto University in Japan. It involves inserting four different genes into the skin cells, causing them to revert to a primordial state similar to embryonic stem cells.

The immediate potential of the method is that it will reveal the chemical and molecular changes that occur in motor neurons before they degenerate. It also will allow researchers to test libraries of chemical compounds on the cells to see if they can intervene in this process.

Because Yamanaka's method uses viruses to ferry the genes into the cells, it can trigger cancer and other undesired effects. Research teams around the world are now looking for alternative methods of reprogramming cells without using viruses. Unless a safer method is found, the technique can't be used to make treatments.

Kevin Eggan, the lead author of the study, said Yamanaka's technique provided a way to proceed with research that he and his colleagues had hoped to conduct by cloning patients' skin cells, the same method used in 1996 to create Dolly the sheep.

Women as Donors

In that technique, the nucleus of a patient's skin cell is inserted into a woman's egg cell whose genetic material has been removed. Eggan said he and other scientists haven't obtained enough egg cells from women to successfully clone human cells because of ethical rules that bar researchers from paying egg donors for their time.

The Harvard Stem Cell Institute, where Eggan works, has spent about $100,000 on newspaper advertisements asking young women to donate their eggs for research. While the promotion generated hundreds of phone calls from interested women, only one provided an egg.

``When told they couldn't be compensated for their time, they rapidly lost interest,'' Eggan said during the call. Women have to spend about 60 hours to provide eggs, partly to undergo uncomfortable and sometimes risky hormone treatments to stimulate the release of multiple eggs, Eggan said.

The new finding shows the skin cells of older patients can be used to make stem cells, even though researchers had been concerned that their age might prevent the process from working. The cells came from sisters who are 82 and 89 years old and are among the oldest living patients with ALS, according to the study.

Eggan said his team also is trying similar work using cells from patients with other forms of ALS.

To contact the reporter on this story: Rob Waters in San Francisco at rwaters5@bloomberg.net.

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